Acrolein and Copper as Competitive Effectors of α‐Synuclein

Autor: Petra Hellwig, Bertrand Vileno, Ikhlas Mohamed Mohamud Ahmed, Enrico Falcone, Peter Faller, Valentina Oliveri, Graziella Vecchio, Francesco Bellia, Youssef El Khoury
Přispěvatelé: Institut de Chimie de Strasbourg, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut de Chimie du CNRS (INC), Laboratoire de Bioélectrochimie et Spectroscopie, Chimie de la matière complexe (CMC), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), University of Catania [Italy], Laboratoire de chimie de coordination (LCC), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Předmět:
medicine.disease_cause
Acrolein
Aggregation
Oligomers
Synuclein
copper
01 natural sciences
Protein Carbonylation
chemistry.chemical_compound
Tandem Mass Spectrometry
immune system diseases
[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology
skin and connective tissue diseases
Chromatography
High Pressure Liquid
ComputingMilieux_MISCELLANEOUS
chemistry.chemical_classification
Effector
amyloid beta-peptides
aggregation
[CHIM.MATE]Chemical Sciences/Material chemistry
[SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biophysics
alpha-Synuclein
musculoskeletal diseases
inorganic chemicals
chemistry.chemical_element
[CHIM.INOR]Chemical Sciences/Inorganic chemistry
010402 general chemistry
Catalysis
Protein Aggregates
synuclein
medicine
Humans
oligomers
Reactive oxygen species
010405 organic chemistry
Organic Chemistry
General Chemistry
Copper
Dynamic Light Scattering
nervous system diseases
0104 chemical sciences
Oxidative Stress
nervous system
chemistry
Biophysics
[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph]
Reactive Oxygen Species
Carbonylation
Oxidative stress
Zdroj: Chemistry-A European Journal
Chemistry-A European Journal, Wiley-VCH Verlag, 2020, 26 (8), pp.1871-1879. ⟨10.1002/chem.201904885⟩
Chemistry (Weinh., Print) 26 (2020): 1871–1879. doi:10.1002/chem.201904885
info:cnr-pdr/source/autori:Falcone, Enrico; Ahmed, Ikhlas M. M.; Oliveri, Valentina; Bellia, Francesco; Vileno, Bertrand; El Khoury, Youssef; Hellwig, Petra; Faller, Peter; Vecchio, Graziella/titolo:Acrolein and Copper as Competitive Effectors of alpha-Synuclein/doi:10.1002%2Fchem.201904885/rivista:Chemistry (Weinh., Print)/anno:2020/pagina_da:1871/pagina_a:1879/intervallo_pagine:1871–1879/volume:26
Chemistry-A European Journal, Wiley-VCH Verlag, 2019, 26 (8), pp.1871-1879. ⟨10.1002/chem.201904885⟩
ISSN: 1521-3765
0947-6539
DOI: 10.1002/chem.201904885
Popis: Mounting evidence supports the role of amyloidogenesis, oxidative stress, and metal dyshomeostasis in the development of neurodegenerative disorders. Parkinson's Disease is characterized by alpha-synuclein (alpha Syn) accumulation and aggregation in brain regions, also promoted by Cu2+. alpha Syn is modified by reactive carbonyl species, including acrolein (ACR). Notwithstanding these findings, the interplay between ACR, copper, and alpha Syn has never been investigated. Therefore, we explored more thoroughly the effects of ACR on alpha Syn using an approach based on LC-MS/MS analysis. We also evaluated the influence of Cu2+ on the protein carbonylation and how the ACR modification impacts the Cu2+ binding and the production of Reactive Oxygen Species (ROS). Finally, we investigated the effects of ACR and Cu2+ ions on the alpha Syn aggregation by dynamic light scattering and fluorescence assays. Cu2+ regioselectively inhibits the modification of His50 by ACR, the carbonylation lowers the affinity of His50 for Cu2+ and ACR inhibits alpha Syn aggregation both in the presence and in the absence of Cu2+.
Databáze: OpenAIRE
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